The major goal of this project is to learn more about the physiology of human motor control using transcranial magnetic stimulation (TMS) and transcranial electrical stimulation (TES). An important theme of this work has been to understand the plasticity of the motor system in a number of circumstances. In our study of hemiplegia after stroke we have been evaluating patients with subcortical lesions. In most of these patients cortical excitability is much reduced (despite no such reduction on functional PET scans). We are beginning some therapeutic trials in stroke rehabilitation and will include physiological studies. In an on-going trial, we are trying to reverse "learned non-use" with appropriate physical therapy. Repetitive TMS (rTMS) delivered to the occipital cortex but not to control positions in early blind subjects disrupts Braille reading indicating that the occipital cortex is necessary for performance of this task in the blind. This result indicates the functional importance of cross-modal plasticity. We have found that 1 Hz rTMS applied to the primary motor area produces dysfacilitation of the primary motor area in the opposite hemisphere. We have completed studies evaluating the nature of the cortical plasticity following ischemic deafferentation of the forearm. The cortex shows a greater reactivity to interventions at this time. TMS is also being used in trials as a possible therapeutic modality; attempts are being made to speed up movement in patients with Parkinson's disease and correct dysmetria in patients with cerebellar ataxia. TMS was used to evaluate the excitability of spinal motoneurons during the cutaneous evoked silent period in intrinsic hand muscles in normal subjects, comparing changes in magnetic evoked potentials with H reflexes, which are susceptible to presynaptic inhibition. The common time course of inhibition of both measures suggests that inhibition through cutaneous pathways occurs by post-synaptic inhibition of motoneurons, rather than interruption of excitatory drive. Some studies are being done in psychiatric disorders. In 12 patients with obsessive- compulsive disorder (OCD), we have found abnormal absence of intracortical inhibition at short (3-6 ms) intervals. In a study of 11 depressed patients, we have found lateralized effects of a single rTMS treatment which agree with the findings of more prolonged treatment studies and are opposite to the mood effects of rTMS in normals.